Essential role of the p38 mitogen-activated protein kinase pathway in tissue factor gene expression mediated by the phosphatidylserine-dependent antiprothrombin antibody.
Essential role of the p38 mitogen-activated protein kinase pathway in tissue factor gene expression mediated by the phosphatidylserine-dependent antiprothrombin antibody.
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p38 丝裂原激活蛋白激酶途径在磷脂酰丝氨酸依赖性抗凝血酶原抗体介导的组织因子基因表达中的重要作用。
DOI：
10.1093/rheumatology/ket234
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Atsumi T.
中科院分区：
文献类型：
--
作者：
Oku K;Amengual O;Zigon P;Horita T;Yasuda S;Atsumi T.
目的：探讨磷脂酰丝氨酸依赖性抗凝血酶原抗体（aPS/PT）对促凝血细胞中组织因子（TF）表达及信号转导通路的影响。方法：健康人外周血单个核细胞（PBMCs），鼠单核细胞RAW 264.7细胞和人脐静脉内皮细胞（HUVEC）在凝血酶原存在下，用从aPS/PT阳性的APS患者获得的IgG级分或鼠单克隆aPS/PT抗体231 D处理。采用实时荧光定量PCR检测TF mRNA水平。通过凝血试验测定TF功能（通过促凝血活性测定）。通过流式细胞术分析测定处理的细胞表面上的231 D结合。使用阵列测定进行细胞内信号传导蛋白的磷酸化的筛选。用ELISA法定量分析p38 MAPK磷酸化水平，并以SB 203580作为p38 MAPK的特异性抑制剂。p38 MAPK的特异性siRNA被用于knockdown assay.Results。APS患者和231 D的IgG组分诱导TF mRNA过表达，并缩短凝血酶原存在下的细胞凝血时间。231 D部分在结合到RAW264.7细胞的细胞表面后诱导p38 MAPK的磷酸化。结论：aPS/PT通过p38 MAPK磷酸化诱导促凝血细胞TF表达。这种现象可能与APS的致血栓性有关。
Objective.The aim of this study was to investigate the effects of phosphatidylserine-dependent antiprothrombin antibody (aPS/PT) on the expression of tissue factor (TF) and the signal transduction pathway in procoagulant cells.Methods.Peripheral blood mononuclear cells (PBMCs) from a healthy donor, murine monocyte RAW264.7 cells and human umbilical vein endothelial cells (HUVECs) were treated with either IgG fractions obtained from APS patients who were positive for aPS/PT or a murine monoclonal aPS/PT antibody, 231D, in the presence of prothrombin. The levels of TF mRNA were measured using real-time PCR. TF function, as measured by procoagulant activity, was determined with a clotting assay. 231D binding on the surface of treated cells was determined by flow cytometric analysis. Screening for phosphorylation of intracellular signalling proteins was conducted using an array assay. Phosphorylation of p38 MAPK was quantitatively analysed with ELISA, and SB203580 was used as a specific inhibitor of p38 MAPK. Specific siRNA for p38 MAPK was used for the knockdown assay.Results.The IgG fractions from APS patients and 231D induced TF mRNA overexpression and shortening of coagulation time in cells in the presence of prothrombin. The 231D moiety induced phosphorylation of p38 MAPK after binding to the cell surface of RAW264.7 cells. SB203580 or p38 siRNA significantly hampered TF overexpression.Conclusion.Expression of TF in procoagulant cells was induced by aPS/PT via p38MAPK phosphorylation. This phenomenon may be correlated with the thrombogenicity of APS.
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3.6
作者：
I. Marai;H. Carp;S. Shai;R. Shabo;G. Fishman;Y. Shoenfeld
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DOI：
10.1002/art.21009
发表时间：
2005
期刊：
Arthritis and rheumatism.
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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